Natural killer (NK) cells are generally regarded as innate effector cells for killing virally-infected and transformed cells. Joint research by the labs of Professor Fan and Professor Fu demonstrated that the TNF superfamily member, LIGHT, is a critical ligand for theactivation of NK cells. They showed that Herpes virus entry mediator (HVEM) is expressed on NK cells, and its engagement with LIGHT mediates NK-cell activation. Both NK and CD8+ cells were shown to be essential but not sufficient for the rejection of tumors because mice lacking either population failed to reject the tumor. Interestingly, activated NK cells did not kill tumors directly but facilitated the priming of tumor-specific CD8+ T cells in an IFN-gamma-dependent manner. Conversely, intra-tumor depletion of either NK cells or IFN-gamma during tumor progression was shown to disrupt CD8+ cell-mediated tumor rejection, suggesting that the tumor is the essential site for the crosstalk between NK and CD8+ cells. Furthermore, IFNG-deficient NK cells failed to effectively activate CD8+ T cells, suggesting IFN-gamma plays an important role in NK-mediated activation of cytotoxic T lymphocytes (CTLs). These findings established a direct role for LIGHT in NK activation/expansion and a critical helper role of activated NK cells in priming CD8+ T cells and breaking Tcell tolerance at the tumor site.

This work was published on BLOOD (2006,107(4): 1342-1351).